Protracted synaptogenesis after activity-dependent spinogenesis in hippocampal neurons

Max Planck Institute of Neurobiology, 82152 München-Martinsried, Germany.
The Journal of Neuroscience : The Official Journal of the Society for Neuroscience (Impact Factor: 6.75). 08/2007; 27(30):8149-56. DOI: 10.1523/JNEUROSCI.0511-07.2007
Source: PubMed

ABSTRACT Activity-dependent morphological plasticity of neurons is central to understanding how the synaptic network of the CNS becomes reconfigured in response to experience. In recent years, several studies have shown that synaptic activation that leads to the induction of long-term potentiation also drives the growth of new dendritic spines, raising the possibility that new synapses are made. We examine this directly by correlating time-lapse two-photon microscopy of newly formed spines on CA1 pyramidal neurons in organotypic hippocampal slices with electron microscopy. Our results show that, whereas spines that are only a few hours old rarely form synapses, older spines, ranging from 15 to 19 h, consistently have ultrastructural hallmarks typical of synapses. This is in agreement with a recent in vivo study that showed that, after a few days, new spines consistently form functional synapses. In addition, our study provides a much more detailed understanding of the first few hours after activity-dependent spinogenesis. Within tens of minutes, physical contacts are formed with existing presynaptic boutons, which slowly, over the course of many hours, mature into new synapses.

  • [Show abstract] [Hide abstract]
    ABSTRACT: Longitudinal imaging studies of neuronal structures in vivo have revealed rich dynamics in dendritic spines and axonal boutons. Spines and boutons are considered to be proxies for synapses. This implies that synapses display similar dynamics. However, spines and boutons do not always bear synapses, some may contain more than one, and dendritic shaft synapses have no clear structural proxies. In addition, synaptic strength is not always accurately revealed by just the size of these structures. Structural and functional dynamics of synapses could be studied more reliably using fluorescent synaptic proteins as markers for size and function. These proteins are often large and possibly interfere with circuit development, which renders them less suitable for conventional transfection or transgenesis methods such as viral vectors, in utero electroporation, and germline transgenesis. Single cell electroporation (SCE) has been shown to be a potential alternative for transfection of recombinant fluorescent proteins in adult cortical neurons. Here we provide proof of principle for the use of SCE to express and subsequently image fluorescently tagged synaptic proteins over days to weeks in vivo.
    Frontiers in Neuroanatomy 04/2015; 9(36). DOI:10.3389/fnana.2015.00036 · 4.18 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Synaptic plasticity mechanisms are usually discussed in terms of changes in synaptic strength. The capacity of excitatory synapses to rapidly modify the membrane expression of glutamate receptors in an activity-dependent manner plays a critical role in learning and memory processes by re-distributing activity within neuronal networks. Recent work has however also shown that functional plasticity properties are associated with a rewiring of synaptic connections and a selective stabilization of activated synapses. These structural aspects of plasticity have the potential to continuously modify the organization of synaptic networks and thereby introduce specificity in the wiring diagram of cortical circuits. Recent work has started to unravel some of the molecular mechanisms that underlie these properties of structural plasticity, highlighting an important role of signaling pathways that are also major candidates for contributing to developmental psychiatric disorders. We review here some of these recent advances and discuss the hypothesis that alterations of structural plasticity could represent a common mechanism contributing to the cognitive and functional defects observed in diseases such as intellectual disability, autism spectrum disorders and schizophrenia.
    Frontiers in Neuroanatomy 11/2014; 8:123. DOI:10.3389/fnana.2014.00123 · 4.18 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Spines are small protrusions arising from dendrites that receive most excitatory synaptic input in the brain. Dendritic spines represent dynamic structures that undergo activity-dependent adaptations, for example, during synaptic plasticity. Alterations of spine morphology, changes of spine type ratios or density have consequently been found in paradigms of learning and memory, and accompany many neuropsychiatric disorders. Polymorphisms in the gene encoding KIBRA, a protein present in kidney and brain, are linked to memory performance and cognition in humans and mouse models. Deletion of KIBRA impairs long-term synaptic plasticity and postsynaptic receptor recycling but no information is available on the morphology of dendritic spines in null-mutant mice. Here, we directly examine the role of KIBRA in spinous synapses using knockout mice. Since KIBRA is normally highly expressed in neocortex and hippocampus at juvenile age, we analyze synapse morphology in intact tissue and in neuronal cultures from these brain regions. Quantification of different dendritic spine types in Golgi-impregnated sections and in transfected neurons coherently reveal a robust increase of filopodial-like long protrusions in the absence of KIBRA. While distribution of pre- and postsynaptic marker proteins, overall synapse ultrastructure and density of asymmetric contacts were remarkably normal, electron microscopy additionally uncovered less perforated synapses and spinules in knockout neurons. Thus, our results indicate that KIBRA is involved in the maintenance of normal ratios of spinous synapses, and may thus provide a structural correlate of altered cognitive functions when this memory-associated molecule is mutated.
    Frontiers in Neuroanatomy 02/2015; 9:13. DOI:10.3389/fnana.2015.00013 · 4.18 Impact Factor